Phosphorus is an essential element in the maintenance of life and plays very important roles in various physiological functions. Phosphorus is taken up in the form of phosphate through the gastrointestinal tract from food, and most of the phosphorous is excreted by incorporation into urine, whereby its total amount in a living body is maintained and regulated. It is known that in the process of formation of urine, substantially most of phosphate is filtered at the glomerulus and only a required amount thereof is reabsorbed in the tubules. Accordingly, if the filtration ability of the glomerulus decreases as renal failure progresses, excretion of phosphorus becomes insufficient. Thus, an abnormal increment of the serum phosphorus concentration, that is, hyperphosphatemia develops.
Hyperphosphatemia induces an concentration increase of FGF-23 in the blood which is a promoting factor for phosphorous excretion in urine, or that of parathyroid hormone (iPTH). An abnormal rise in iPTH is one of the complications of renal failure, called hyperparathyroidism, which also causes ectopic calcification or the like through the activation of bone metabolism. In this way, hyperphosphatemia becomes one of the causes or aggravating factors of other complications associated with decreased renal function, through the action of compensatory functions of the body accompanying hyperphosphatemia.
As described above, it is thought that hyperphosphatemia inducing various complications of renal failure becomes a cause of decrease in QOL for patients with renal failure due to bone fracture, bone pain, or the like, or the death of patients with renal failure due to cardiovascular diseases caused by calcification of the cardiovascular system. In this regard, hyperphosphatemia becomes a very significant problem in clinical practice.
Currently, for the treatment of hyperphosphatemia, phosphate binders, for example, various calcium salt preparations typically exemplified by precipitated calcium carbonate, a polymer typically exemplified by sevelamer hydrochloride, or metal salt preparations such as lanthanum carbonate, aluminum hydroxide, an iron preparation, and the like are used for the purpose of inhibiting the phosphorus absorption from the gastrointestinal tract. These drugs, however, have various problems, such as poor dose adherence due to the requirement for several grams per day, gastrointestinal symptoms such as constipation/diarrhea, and the like, elevated concentration of calcium in the serum, accumulation of various metals, and the like, and thus, there is a demand for development of a novel agent for treating hyperphosphatemia having modifications of these weak points (see, for example, Non-Patent Document 1).
On the other hand, it is thought that absorption and excretion of phosphorus are associated with phosphate transporters presenting on the brush border membrane of the gastrointestinal tract and kidney tubules. A number of the phosphate transporters have been reported, but among them, NPT-IIb and NPT-IIa play a major role in phosphate absorption in the gastrointestinal tract and phosphate reabsorption in the kidney, respectively. Moreover, these molecules have also been reported as a sodium and phosphate cotransporter. From this, it is thought that the phosphorus absorption from the gastrointestinal tract can be inhibited by inhibition of the function of NPT-IIb (see, for example, Non-Patent Document 2).
From the above, it is suggested that an NPT-IIb inhibiting agent is promising as a medicament for treating hyperphosphatemia with novel mechanism of actions which will replace various phosphate binders that have currently been used in clinical practice.
In Patent Document 1, there is disclosed a compound having an NPT-IIb inhibitory action, which is represented by the general formula (A) and specifically, a compound having a tetrahydrobenzothiophene skeleton is also disclosed, but its substituents at the 2-position and the 3-position are each different from those of the compound of the present invention. That is, from a viewpoint that its substituent at the 3-position is a hydrazinocarbonyl group, it is clearly different from the compound of the present invention in which the substituent at the 3-position is a phenylcarbamoyl group. Further, a substituent at the 2-position is a benzoylamino group, but the substituents of this benzene ring do not include a sulfamoyl group as in the compound of the present invention.

(wherein A represents a 5- to 9-membered unsaturated heterocycle or the like, R5 represents an aryl group or the like, R101 and R102, combined together, represent ═O, or the like, and Z represents a compound represented by the following formula (i), (ii), or (iii). For the other symbols in the formula, refer to the corresponding patent publications).

Furthermore, in Patent Documents 2 and 3, there are disclosed compounds having a NPT-IIb inhibitory action, which have a triazole skeleton and a quinazolinone skeleton, respectively, but there is not disclosed a compound having a tetrahydrobenzothiophene skeleton as in the compound of the present invention.
In Patent Document 4, there is disclosed a compound represented by the general formula (B), but there is not disclosed a compound in which the substituent at the 2-position of a tetrahydrobenzothiophene ring is a sulfamoylbenzoylamino group as in the compound of the present invention.

(wherein R2 represents an optionally substituted phenylamino, or the like, R3 represents an optionally substituted phenyl, or the like, and n represents 1 or the like. For the other symbols in the formula, refer to the corresponding patent publications.)
In Patent Document 5, for example, there is disclosed a compound represented by the formula (C) or the like, but there is neither disclosed a compound having phenyl instead of cyclopropyl as a substituent of carbamoyl, which is a substituent at the 3-position of the tetrahydrobenzothiophene ring nor a compound having a sulfamoyl group as a substituent of a benzene ring of a benzoylamino group, which is a substituent at the 2-position.

In Patent Document 6, there is disclosed a compound represented by the formula (D) or the like, in Patent Document 7, there is disclosed a compound represented by the formula (E) or the like, and in Patent Document 8, there is disclosed a compound represented by the formula (F) or the like. However, there is not disclosed a compound having a sulfamoyl group as a substituent of a benzene ring of a benzoylamino group, which is a substituent at the 2-position of a tetrahydrobenzothiophene ring.

In Patent Document 9, for example, there is disclosed a compound represented by the formula (G) or the like, but there is neither disclosed a compound having a benzene ring as a substituent of carbamoyl, which is a substituent at the 3-position of the tetrahydrobenzothiophene ring nor a compound having a sulfamoyl group as a substituent of benzene ring of a benzoylamino group, which is a substituent at the 2-position.

In Patent Document 10, there is disclosed a compound represented by the formula (H) or the like, but there is neither disclosed a compound having phenyl as a substituent of carbamoyl which is a substituent at the 3-position of the tetrahydrobenzothiophene ring nor a compound having sulfamoylphenyl instead of cyclobutyl of a cyclobutylcarbonylamino group which is a substituent at the 2-position.

In Patent Document 11, there is disclosed a compound represented by the general formula (K-a), but it is different from the compound of the present invention in that it does not include a tetrahydrobenzothiophene skeleton. There is further disclosed a compound represented by the general formula (K-b), which can include a tetrahydrobenzothiophene skeleton. However, such a compound in which the substituent at the 2-position is a substituted carbamoyl group is different from the compound of the present invention in which the substituent at the 2-position is a substituted carbonylamino group, and such a compound in which the substituent at the 3-position is a pyrrolidylcarbonylamino group is also different from the compound of the present invention in which the substituent at the 3-position is a phenylcarbamoyl group.

(wherein X represents S or O, and R1 represents —NH(C1-C4 alkyl), the following group:

or the like. R2 represents C1-C10 alkyl, C3-C8 cycloalkyl, phenyl, 5 to 7-membered heteroaryl, or the like, k represents an integer of 2 to 4, R3 represents optionally substituted phenyl, or the like, and n represents an integer of 0 to 4. For the other symbols in the formula, refer to the corresponding patent publications).
In Patent Document 12, there is disclosed a compound represented by the general formula (L), but such a compound which has a tetrahydrothieno[2,3-c]pyridine skeleton is different from the compound of the present invention which has a tetrahydrobenzothiophene skeleton. In addition, there is not specifically disclosed a compound in which the substituent at the 2-position is a phenylaminocarbonyl group.

(wherein R2 represents arylaminocarbonyl in which aryl is optionally substituted, or the like. For the other symbols in the formula, refer to the corresponding patent publications).
In Patent Document 13, there is disclosed a compound represented by the formula (M-a) or the formula (M-b), but there is not disclosed a compound having a benzene ring as a substituent of carbamoyl, which is a substituent at the 3-position of the tetrahydrobenzothiophene ring.

Further, in Patent Documents 4 to 13, it is neither suggested nor disclosed that the compound has an NPT-IIb inhibitory action or is used for preventing or treating hyperphosphatemia.
In addition, there is a compound represented by a formula (N), the formula (O) or the formula (P) as a compound known according to the database. The compound represented by the formula (N) or the formula (O) does not have a benzene ring as a substituent of carbamoyl, which is a substituent at the 3-position of the tetrahydrobenzothiophene ring. Further, the compound represented by the formula (P) is different from the compound of the formula (I). In addition, it is neither suggested nor disclosed that the compound has an NPT-IIb inhibitory action or is used for preventing or treating hyperphosphatemia.
